Crystalline form of 2-((1′-n-hexyloxy) ethyl)-2-divinyl-pyropheophorbide-a and method for preparing thereof

Abstract

The present invention provides a crystalline form of HPPH (2-((1′-n-hexyloxy)ethyl)-2-divinyl-pyropheophorbide-a): The crystalline form can be characterized by an X-ray powder diffraction (XRD) pattern and differential scanning calorimeter (DSC) pattern. The present invention also provides a method for preparing the crystalline form of HPPH.

The invention claimed is:  
     
       1. A method for preparing the crystalline form of 2-((1′-n-hexyloxy) ethyl)-2-divinyl-pyropheophorbide-a (HPPH) characterized by at least one of the features set forth below:
 (1) characteristic peaks (2θ) of X-ray powder diffraction (XRD) pattern being: (2θ±0.2) 5.46°, 6.02°, 13.95°, 18.03°, 24.01°, 24.49°; 
 (2) characteristic peak of differential scanning calorimeter (DSC) pattern: a characteristic endothermic peak being at 201.2° C., comprising the four steps set forth below: 
 1) dissolving an HPPH sample into a polar organic solvent; 
 2) adding a non-polar solvent to promote crystallization of the HPPH; 
 3) mixing the mixture, then continuously stirring or sitting undisturbed for 1 to 8 hrs; 
 4) isolating the obtained crystal, 
 wherein, the polar solvent is selected from ethyl acetate or acetone, the non-polar solvent is selected from n-hexane or n-heptane, and the step of isolating comprises filtering and drying. 
 
     
     
       2. The method according to  claim 1 , characterized by the polar solvent being acetone. 
     
     
       3. The method according to  claim 1 , characterized by the non-polar solvent being n-heptane. 
     
     
       4. The method according to  claim 1 , characterized by an amount of the polar solvent (volume) being 3 to 15 times of the mass of the HPPH sample, wherein the unit of the ratio of volume to mass is ml/g. 
     
     
       5. The method according to  claim 1 , characterized by an amount of the non-polar solvent (volume) being 3 to 15 times of the volume of the polar solvent. 
     
     
       6. The method according to  claim 1 , characterized by the dissolving temperature being 0° C. to 60° C., the temperature in step 3) being 0° C. to 30° C. 
     
     
       7. The method according to  claim 1 , characterized by the drying temperature being 0° C. to 60° C. 
     
     
       8. The method according to  claim 1 , characterized by an amount of the polar solvent (volume) being 5 to 10 times of the mass of the HPPH sample, wherein the unit of the ratio of volume to mass is ml/g. 
     
     
       9. The method according to  claim 1 , characterized by an amount of the non-polar solvent (volume) being 6 to 10 times of the volume of the polar solvent. 
     
     
       10. The method according to  claim 1 , characterized by the dissolving temperature being 40° C. to 50° C., the temperature in step 3) being 0° C. to 10° C. 
     
     
       11. The method according to  claim 1 , characterized by the drying temperature being 30° C. to 50° C.